Impaired IgG Production in the Lungs of HIV-Infected Individuals

Twigg, Homer L.; Spain, Blake A.; Soliman, Diaa M.; Bowen, Linda K.; Heidler, Kathleen M.; Wilkes, David S.

doi:10.1006/cimm.1996.0142

Cited by 29 publications

(27 citation statements)

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“…When using the latter mAb-iFt complex as an i.n. immunogen for either BALB/c or C57BL/6 strains of mice, and subsequently challenging these mice with F. tularensis LVS at 4 ϫ LD 50 14 days postimmunization, we observed significantly better protection (100%) compared with iFt (between 50 and 65%) (Fig. 1, B and C).…”

Section: Enhanced Protection Against F Tularensis Lvs Challenge Follmentioning

confidence: 80%

“…A third potential explanation involves the production of TGF-␤. Studies have demonstrated that the secretion of TGF-␤ can differentially regulate IgA vs IgG production, suppressing the latter while not effecting or enhancing IgA production (50,51). Thus, investigations are now underway to address each of these possibilities.…”

Section: Discussionmentioning

confidence: 99%

“…would enhance protection against the highly virulent form of F. tularensis, SchuS4. In this case, mice were challenged with 10 -20 ϫ LD 50 to increase the significance of any protection observed. When immunizing C57BL/6 mice with mAb-iFt made from F. tularensis LVS, we FIGURE 6.…”

Section: Immunization With Mab-ift Generates Protection Against the Hmentioning

confidence: 99%

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Utilization of Fc Receptors as a Mucosal Vaccine Strategy against an Intracellular Bacterium, Francisella tularensis

Rawool

Bitsaktsis

et al. 2008

The Journal of Immunology

179

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Numerous studies have demonstrated that targeting Ag to Fc receptors (FcR) on APCs can enhance humoral and cellular immunity. However, studies are lacking that examine both the use of FcR-targeting in generating immune protection against infectious agents and the use of FcRs in the induction of mucosal immunity. Francisella tularensis is a category A intracellular mucosal pathogen. Thus, intense efforts are underway to develop a vaccine against this organism. We hypothesized that protection against mucosal infection with F. tularensis would be significantly enhanced by targeting inactivated F. tularensis live vaccine strain (iFt) to FcRs at mucosal sites, via intranasal immunization with mAb-iFt complexes. These studies demonstrate for the first time that: 1) FcR-targeted immunogen enhances immunogen-specific IgA production and protection against subsequent infection in an IgA-dependent manner, 2) FcγR and neonatal FcR are crucial to this protection, and 3) inactivated F. tularensis, when targeted to FcRs, enhances protection against the highly virulent SchuS4 strain of F. tularensis, a category A biothreat agent. In summary, these studies show for the first time the use of FcRs as a highly effective vaccination strategy against a highly virulent mucosal intracellular pathogen.

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Section: Enhanced Protection Against F Tularensis Lvs Challenge Follmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Utilization of Fc Receptors as a Mucosal Vaccine Strategy against an Intracellular Bacterium, Francisella tularensis

Rawool

Bitsaktsis

et al. 2008

The Journal of Immunology

179

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“…There are conflicting data regarding bronchoalveolar lavage (BAL) levels of total IgG in HIV-infected adults [11,12], but levels of pneumococcal-specific IgG have not been reported. We therefore tested the hypothesis that the susceptibility of HIV-infected adults to IPD is due to a local failure of pulmonary immunoglobulin production.…”

mentioning

confidence: 99%

Pulmonary Immunoglobulin Responses toStreptococcus pneumoniaeAre Altered but Not Reduced in Human Immunodeficiency Virus–Infected Malawian Adults

et al. 2003

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We tested the hypothesis that human immunodeficiency virus (HIV)-infected adults have a specific defect in anti-pneumococcal capsular polysaccharide (Pn-specific) immunoglobulin (Ig) in fluid obtained from the lower respiratory tract. Higher levels of total IgG and IgM were present in bronchoalveolar lavage samples from HIV-infected subjects than in those from HIV-uninfected subjects. Pn-specific IgG and IgM in bronchoalveolar lavage samples were not significantly different between HIV-infected and -uninfected subjects. After pneumococcal infection, HIV-infected patients had higher bronchoalveolar lavage levels of Pn-specific IgG than HIV-infected patients without recent infection (geometric means, 387 vs. 30 ng/mL, P=.001).

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“…Initially, the viral load in alveolar macrophages was thought to be unusually high and closely related to the clinical status of the patient [52] but it now seems that alveolar macrophages contain a similar viral load to other cells of the macrophage lineage [53]. Nevertheless, HIV infection affects activation [54], receptor expression [55], accessory cell function [56], cytokine production [57], regulatory functions [58,59] and phagocytosis [60] in alveolar macrophages. Given the pivotal role of the alveolar macrophage in regulating pulmonary defence against pneumococci, we hypothesised that a failure in alveolar macrophage function might contribute to the susceptibility of HIV-infected adults to pneumococcal infection.…”

Section: Hiv Pneumococcal Infections and Alveolar Macrophagesmentioning

confidence: 99%

Respiratory infections: Proceedings of the Eighth Liverpool Tropical School Bayer Symposium of Microbial Disease held on 3 February 2001

Cant

Gordon

Read

et al. 2002

Journal of Medical Microbiology

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Impaired IgG Production in the Lungs of HIV-Infected Individuals

Cited by 29 publications

References 0 publications

Utilization of Fc Receptors as a Mucosal Vaccine Strategy against an Intracellular Bacterium, Francisella tularensis

Utilization of Fc Receptors as a Mucosal Vaccine Strategy against an Intracellular Bacterium, Francisella tularensis

Pulmonary Immunoglobulin Responses toStreptococcus pneumoniaeAre Altered but Not Reduced in Human Immunodeficiency Virus–Infected Malawian Adults

Respiratory infections: Proceedings of the Eighth Liverpool Tropical School Bayer Symposium of Microbial Disease held on 3 February 2001

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